When to draw voriconazole (antifungal medication) levels?

When to Draw Voriconazole Levels

Draw the first voriconazole trough level between 2-5 days after starting therapy, then repeat the following week to confirm steady-state, and continue monitoring with any clinical changes, dose adjustments, or suspected toxicity. 1

Initial Level Timing

• Obtain the first plasma trough concentration 2-5 days after initiating voriconazole therapy to assess whether therapeutic targets are being achieved 1, 2
• Steady-state concentrations are typically reached approximately 5 days after both intravenous and oral administration without a loading dose 3
• When a loading dose is administered, steady-state is reached within 24 hours, but initial monitoring should still occur at 2-5 days to confirm maintenance dosing adequacy 3

Timing Relative to Dose Administration

• Voriconazole has a half-life of 6-8 hours, and blood levels vary 2-fold over a 12-hour dosing interval 1
• The timing of blood specimen collection in relationship to the most recent dose is essential - always draw trough levels (immediately before the next scheduled dose) 1
• This differs from itraconazole, where timing is not critical due to its longer 24-hour half-life 1

Follow-Up Monitoring Schedule

• Repeat the level the following week (approximately day 7-12) to confirm the patient remains in the therapeutic range 1, 2
• Continue monitoring until steady-state level in the therapeutic range is confirmed 1, 2
• After achieving stable therapeutic levels, routine monitoring may be less frequent unless clinical changes occur 1

Indications for Repeated Level Monitoring

Draw additional levels whenever any of the following occur: 1, 2

• Changes in the patient's clinical condition (worsening infection, new symptoms)
• Addition or discontinuation of concomitant medications known to interact with voriconazole (phenytoin, rifampin, proton pump inhibitors, glucocorticoids) 2
• Suspected toxicity (visual disturbances, hepatotoxicity, neurotoxicity, photosensitivity)
• Changes in hepatic or renal function
• After any dose adjustment - recheck level in 2-5 days 4

Special Population Considerations

Pediatric Patients

• Therapeutic drug monitoring is strongly recommended in children due to much higher rates of drug elimination and potential for underdosing 1, 2
• Children require more frequent monitoring as they often need higher and more frequent dosing adjustments 5
• Serial monitoring in pediatric patients improves treatment response and prevents unnecessary drug discontinuation 5

CNS Infections

• For patients with CNS fungal infections, use the same timing (2-5 days initially, then weekly) but target a higher therapeutic range of 2-6 mg/L 2
• More intensive monitoring may be warranted given the severity of infection and need for higher target levels 2

Target Therapeutic Ranges

• Standard infections: Target trough concentration of 1-5.5 mg/L 1
• Severe infections (CNS, disseminated disease, pathogens with elevated MICs): Target trough concentration of 2-6 mg/L 1, 2
• Prophylaxis: Target trough concentration of 1-5.5 mg/L 1

Common Pitfalls to Avoid

• Do not draw levels too early (before day 2) - voriconazole exhibits nonlinear pharmacokinetics and requires time to approach steady-state 3
• Do not draw random levels - always obtain trough concentrations due to significant variation over the dosing interval 1
• Do not assume therapeutic levels persist without monitoring - 46% of voriconazole levels in real-world practice were non-therapeutic, supporting the need for routine TDM 6
• Do not delay dose adjustments - when levels are subtherapeutic, increase the daily dose by approximately 50% and recheck in 2-5 days 2